@article{692184f41efb4dc3ae2fc4048786bcf6,
title = "High concordance of ELISA and neutralization assays allows for the detection of antibodies to individual AAV serotypes",
abstract = "Prescreening of participants in clinical trials that use adeno-associated virus (AAV) vectors is required to identify naive participants, as preexisting neutralizing antibodies can limit the efficacy of AAV gene therapies. The presence of antibodies to individual AAV serotypes is typically detected by neutralization assay. To streamline the screening process, we compared an ELISA-based screening method with a neutralization assay for the detection of antibodies against AAV1, AAV8, and AAV9 in a collection of 50 rhesus macaque sera and 20 human sera. We observed a high level of concordance between the two assays (Pearson r > 0.8) for all three serotypes in both sample sets. We thus investigated pre- vs post-vector inoculation sera samples from rhesus macaques that received AAV1 or AAV8 vector inoculations for cross-reactive anti-AAV antibodies. All 12 macaques seroconverted to the vector they received, but many also reacted to the other serotypes. Our results validate an easy-to-use ELISA for reliable detection of antibodies to individual serotypes of AAV. Our results also demonstrate that an antibody response post-AAV inoculation may partially cross-react with other AAV serotypes. Overall, these results suggest that either assay can be used by academic labs for prescreening samples for preexisting anti-AAV antibodies.",
keywords = "AAV, ELISA, adeno-associated virus, capsid, gene therapy, neutralization assay, serotype",
author = "Gardner, {Matthew R.} and Mendes, {Desiree E.} and Muniz, {Claudia P.} and Martinez-Navio, {Jos{\'e} M.} and Fuchs, {Sebastian P.} and Guangping Gao and Desrosiers, {Ronald C.}",
note = "Funding Information: We would like to the thank William Lauer for his technical expertise and coordinating of sample distribution; Eva Rakasz for rhesus macaque sample collection and distribution; and Meredith E. Davis-Gardner for her insights and comments on the manuscript. The graphical abstract was created using BioRender.com . This work was supported by the Emory University Molecules and Pathogens to Populations and Pandemics (MP3) Initiative and by NIH grants R00AI138860 (M.R.G.), R01AI098446 (R.C.D.), and U19AI149646 (R.C.D.). Funding Information: We would like to the thank William Lauer for his technical expertise and coordinating of sample distribution; Eva Rakasz for rhesus macaque sample collection and distribution; and Meredith E. Davis-Gardner for her insights and comments on the manuscript. The graphical abstract was created using BioRender.com. This work was supported by the Emory University Molecules and Pathogens to Populations and Pandemics (MP3) Initiative and by NIH grants R00AI138860 (M.R.G.), R01AI098446 (R.C.D.), and U19AI149646 (R.C.D.). M.R.G. designed the study and performed experiments. D.E.M. and C.P.M. performed experiments. J.M.M.-N. provided critical samples for analysis. S.P.F. performed data analysis. G.G. provided critical reagents. R.C.D. designed and supervised the study. M.R.G. and R.C.D. wrote the manuscript with input and approval from all the coauthors. M.R.G. is a co-founder and consultant for Emmune, Inc. M.R.G. is an inventor on patents with potential royalties licensed to Emmune, Inc. G.G. is a co-founder of Voyager Therapeutics and Aspa Therapeutics and holds equity in both companies. G.G. is an inventor on patents with potential royalties licensed to Voyager Therapeutics, Aspa Therapeutics, and other biopharmaceutical companies. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = mar,
day = "10",
doi = "10.1016/j.omtm.2022.01.003",
language = "English (US)",
volume = "24",
pages = "199--206",
journal = "Molecular Therapy - Methods and Clinical Development",
issn = "2329-0501",
publisher = "Nature Publishing Group",
}